IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: X-linked agammaglobulinemia

1 .Inheritance

X-linked Recessive

2. Gene Name

BTK

3. Protein Name

Tyrosine-protein kinase BTK

4. Chromosomal Location

Xq21.33-q22

5. Protein Sequence

>sp|Q06187|BTK_HUMAN Tyrosine-protein kinase BTK OS=Homo sapiens OX=9606 GN=BTK PE=1 SV=3
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL
RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS
HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE
YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK
EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN
YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK
WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG
CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF
GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER
FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

6. Gene Sequence

>NC_000023.11:c101390796-101349450 Homo sapiens chromosome X, GRCh38.p14 Primary Assembly

TTCGTCACTTTATCTCTTTTGGTGGACTCTGCTACGTAGTGGCGTTCAGTGAAGGGAGCAGTGTTTTTCC

CAGATCCTCTGGCCTCCCCGTCCCCGAGGGAAGCCAGGACTAGGGTCGAATGAAGGGGTCCTCCACCTCC

ACGTTCCATTCCTGTTCCACCTCAAGGTCACTGGGAACACCTTTCGCAGCAAACTGCTAATTCAATGAAG

ACCTGGAGGGAGCCAATTGTTCCAGTTCATCTATCACATGGCCAGTTGGTCCATTCAACAAATGGTTATT

GGATGCCCATTATGTGGCAGGCACTGTTCCGGGGGAGAGGTACAGTAATCTAATAGGCTTATAAATGTGC

AATTATGAACTAAGTACTTTGAAGAAAAGGAACAATGATTGGCATTAAAGCAGCACCCTTCTGTTGAGGG

AGTAAGTCAGCAGCTCTAGGTTCTGAAAAGTGACAATGAAATTGTTTGGCTCCTGTAATAGCAATCATCA

AGCCTAGAAGTAGAAAGTACCTAGCGGCTCTTCCCTTCCTTGCAAACCTGGCAGAAGGCATATACTAGGT

CTCAAGAGAGTCCAGCATAGAAAGACTTCAGGGTGCTAAACATTTTAAATAGATTGTGTCATACAATTCT

CACAATAATTCTAGGAGACAGGTGGTACTATTATTCTCATTTTACAGATTAAGAAATTGAGGCTGTAGGA

TGTTAAACGATTTGCCCAATGTCAACGGTATTTAGTGAATCTAGGATACAAACCCAAGTAGACTGACTCT

AGAGCCCGCGTTCCTTTAACATTATAAAATATTGCTGTTGTGGCCTGGTAATTATAATAGCTAAAAAAAT

TATGGCGCACTTACTATATGCCAGGCATTCTCCTAACCACCTTACATACTACCCCTTTTAATCCTGACAG

CAACCCCAGGAGGTATATACCAGTATTAGTATTTAACAGGTGAGGAAACTGAGGCACAAGAGATGTTAAG

TTTACTTACCTGAAGTCACACAGGTTGTTATTTTTTTGTGGAGCTGGAATTTGATCCTAGGTAGTCTAAC

ACTATAGCCTTGCACTTAACCACTACATCATACAAAGGAAGCAGGGGCATCTGCAGTGTAGAGGATGGTG

AGGAGACAGAATTGGGCTGAGACACAGGAGGAGGTGGCAGTGGAATAGGGGCTGAAGAACCGTGAGAGTC

TGGGGTATCTTGCTTGCACAACCCTCCAGGAACACGCGTGGGACCTGAGCTGACACTCTGATCACCCCCT

TTTTTGTTGGGTGGTCTCTGGGAATGAGATAATAAATATATTACCACTACCTGCTACATTTCCTGAAAAT

TTCTTTGCCAAACTTCCAGCATTTTCTTTTTCTTTCCAGATTCTTAAGCAATCTCACTGGCCTTTAGGGG

TTTATGTTAGTAACATGGAAATATGAAGACCGTGAACATGGCCCCTCTTCATTTAATCAACCTTAGTTCT

TTCTATCATATCTGGTGTTATGTGGCTTTGTGGGGGTTTTGCTTGTTTTTGTTTACTTAAAAATATTTAA

TTGACAAAAATTGTTTATATTCAAGGTGTACAACATGATGATTTGATATGTGTATACACTGTGTAATGAT

TACCACAGTCAAATTGATTAACACATCTATCATCCATCACCATCCATAGTTACCATGGGGGTGGTGAGGA

CACTTAAAATCTGCTCTCTTATCAAATTTCAATAATACAGTATTATTAACTATGGTCACTATATTGCACA

TTAGATCCCCAGAGCTTATACATCCTATAAGTGAAAGTTTGTACACCAATGCTGACACCGAGGTGGGAGG

ATCGCTTGAGCTGTTCTCTGTTTTGGACATGCTCCTGCTCATTAATTTCCCCTAAGACGAGGCACTCAGA

ACTGAATGCAGGACTCTAGGTGTGGTCTGGCTTTGCAGAGTAAGTGGCATGTTACCTTCCTCTGTCTAGA

TATTTTACTTCCATAAGGAAGCCTCAATGTCACCTTGGCTTTTCTGGAAGCCATGTTAACTGATGACATG

CCTTTTGATTACTATCAGCAAAAACCCCTGAACCATTTTCACAAATGCTACTGCTACTCCACTTTCTCCT

GGAGTCATTTGAAGTTCAAATTTGGGGCCCAATTATGAGACATCACCTTTAGCCCTGGTAAAATACACTT

TGTGGAATTTGGCTTCTCACACCAGGTGATCAAGATCTTTTTGGGAACTAATTGCCCTCTTCTGTCATCC

AGTCTAGCACACAAAGCCTTGCACCATTCATAGACTAACCGGGCTACTTTTTATATTTTCCTCAAAGATG

ATCAATAAAAATGCTGAACAGGATAGCACCAAGAATAGAACCTTATATTGCATTGGGAATCTCTTCAGGT

GACACTCAGCTGTTTATTTGCACTATCTGAGTACAGTCTTTCTGTCAGTATGGATGAGTGTGCTAGGGGA

GTGGTCGTGGGCAGAGGGTGAAGAAAAGCCTACGTCTACTTGCTCTTTTCCCTTGTGCTCCTCTCTCTCT

CTTGTTTAGCTCTCCCATTGGATGCCTATCACCTCCCAGTCCCCACCCCAAGATGGATCTTGAGAAAGGA

CAGGGCATGTGACAACAAGTGGCATAAGACTGAAGAAAAGAGCCTGGGCACGGTGGCTCACGCATGTAAT

CCCAGCACTTTGGGAAGCTGAGGCGGGTGGATCACGAGGTCAGGAGATCGAGACCATCCTGGCTAACATG

GTGAAACCCCGTCTCTACTAAAAATACAAAAAATTAGCCAGGCGTGGTGGCAGGCACCTGTAGTCCCAAC

TACTCAGGAGACTGAGGCAGGACAATGGCGTGAACCCGGGAGGTGGAGCTTGCAGTGAGCCGAGATCATG

CCACTGCACTCCAGCCTGGGCGACAGGGCAAGACTCCGTCTCAAAAAAAAAAAAAACTGAAGAAAAGAGG

AGGGAAGATGAATGCCTGTGGCCAACCCTCAGGCAGGTGAGTGGAACAGCTATTGGGGGTGACTAGCGAA

AGGATAGACGTTGTCAATAAAGTAAGGCAATCATACAACACATGCTGTCCATCTGTCTTGTGCAAATGTG

AGTATCAACCACTCTATCATCAGTCTACAAATACTTTAAATGTTTTTATTTAAAGTCCTGTTGATGGCTG

GGAGAGGTGGCTCACTCCTGTAATCCCTGCATTTTGGGAGGCCAAGGCAGGAGTATCGCTTGAGCCCAGG

AGTTTGAGACCAGCCTGGGCAACATAGTGAAACCCCATCTCTACAAAAAGTAGAAAAATTAGCCCAGCAC

AGTGATGTGTGCCTATAGTCCCAGGTACTAGGGTGACTGAGGTGAGAGGATCACTTGAGCCCAGGAGGTG

GAGGCTGCAGTGAGCCATGATCACGCCACTGCACTCCAACCTGGGCTTCAGAGCAAGACCCTGTCTCAAA

AAAAAAAAAAAAAAAAAAAGGTCCCAGGGCCTGTTGGGGCTTGGGGGTGAGGGGAGGGATCTTAGAGGAT

GGGTCAATAGGTGCAGCAAATCACCATGTCACACATATACCTATGTAACAAACTTGCACCTTCTGCACAT

ATACCCCATTTTTTTTGTTTGCTTGTTTGTTTGTTTTTTAGACAAAATAAAGAAAAAAAAATAAGGTCCT

GTTGACTTAAAACTTCGGATGAAATTGTAGTGGGACCTGTGATCTGTTTCTACATTAGGATACAGTGCCT

TGGGGCAAGGAAATATGGCAGTGCCCGAGGTGTCAAGGTGGGCAGGCAGATCAGTCAGCAGGGGCTCCAC

CATCATGGTCTGCATTCAATACTGGCTGCATTTCCTAGGAGAATCCCTGGGGGAATCATTGCAGTTGGAG

CATAATGTAGGGGGCCCCTGAGAAAACCTCCAGGCTTCAAGTGACATACCTAGTCTGCTTTACCGGTTTA

CAGGACTCAAGAGAAAGGTGGACATTGAGAGTTAATCCCTGAGGCCAAATCTTAAATGGAGAAAGTCAAC

ATCCACAGAAAATGGGGAAGGGCACAAGTATTTCTGTGGGCTTATATTCCGACATTTTTATCTGTAGGGG

AAAAATGCTTTCTTAGAAAATGACTCAGCACGGGGAAGTCTTGTCTCTACCTCTGTCTTGTTTTGTCCTT

TGGGGTCCCTTCACTATCAAGTTCAACTGTGTGTCCCTGAGACTCCTCTGCCCCGGAGGACAGGAGACTC

GAAAAACGCTCTTCCTGGCCAGTCTCTTTGCTCTGTGTCTGCCAGCCCCCAGCATCTCTCCTCTTTCCTG

TAAGCCCCTCTCCCTGTGCTGACTGTCTTCATAGTACTTTAGGTATGTTGTCCCTTTACCTCTGGGAGGA

TAGCTTGATGACCTGTCTGCTCAGGCCAGCCCCATCTAGAGTCTCAGTGGCCCCAGTCATGTTGAGAAAG

GTTCTTTCAAAGATAGACTCAAGATAGTAGTGTCAGAGGTCCCAAGCAAATGAAGGGCGGGGACAGTTGA

GGGGGTGGAATAGGGACGGCAGCAGGGAACCAGATAGCATGCTGCTGAGAAGAAAAAAAGACATTGGTTT

AGGTCAGGAAGCAAAAAAAGGGAACTGAGTGGCTGTGAAAGGGTGGGGTTTGCTCAGACTGTCCTTCCTC

TCTGGACTGTAAGAATATGTCTCCAGGGCCAGTGTCTGCTGCGATCGAGTCCCACCTTCCAAGTCCTGGC

ATCTCAATGCATCTGGGAAGCTACCTGCATTAAGTCAGGACTGAGGTGGGTCTGGGGTATGGCAGGGGCT

GGGCAGCAGCAGCAATGTACCTTGCTTGGGACCCCTAAAAACCAGAGAGACAGCATGGCTGGTGCCATTT

ATCAGCTAGTGGAGGAGGCTGACGGAGGGTGGGAGTGTCATCAGCACAAGGCCCTGGCAGTCCCTTCTGG

TGATTAGAGAGGCCGAAAGGGTCCTTTCCGACAAGGGCTGAGGGTGGGCGGAACAGGAAGAGAAAAATGT

GACATGAGGTGACCATCCGAACAGGTAGCAAATGTTAGAAAGGGGTACCTCTGGCAAACTTAGTGGAAAA

GTAATATTGCAGGGAGCAGTCAGATAAAAACAAGCCCTTCTGTCAAATAGTGCTTGAAGACTCAATAGGG

ATACATGGGTCAATGAAGCCTTTAGAAAAAGAAATACTAAGAGGCAGATTCTCTGAGAACATGGTAAAAG

CTCACGCTCCACGTTATGAAGTTGACCTTTGTGAGCTAGGGAAAGGCCTGGCTAGGCCAGGGTGTAGGCT

ACCTGCCTTGAGCTGTACCAGGCCAAATGTCGCCAGGGTCAGAGCTGGCTTATTAAAGGACTGTGTGGAA

GCTGTGCCAACCTCGTGGTAACAATGGGTAAAAGACTGGGCCAGGAGAAAGCAGCCTCTGCCTCAGCCCA

GACAGTGCGGCCAACCCTTGAGGTTGTGGCAAAGGTTTCTCCTCTTACCATTGCCCTCCATGTGCATGGC

TTGCTTTTCTCTTGTCTTCATTATTTCTCCTTTCCTTTCCTCCTCTCCAACCTCCTCCTCTTCCCACTCA

TCCTCTTTTCTCTACCTATATCCCCTCTTCATTATACCCTCCTCTGTTCTGTTGATTACCAGACCCTGAC

ATACAGTTAGCACTTAACAAATAATTGCCGAATTGCATTGACTTTTTCTTGCTCCTTTCTTCCCCCGCTC

TTTTCCCTTTTCCTTTCCCTTTCCATTTCCTCCTCCCTGCCTGCCTAGCACCTTCCCCATAAGGTGGTTG

TGAGCAGTAAATGTGCAAATACATGTAAAGCTTTTAAAACAGGGCCTGGCAATAGTAAGTGCTGGATCTC

AGTATTTGCTATAATTTTTACTCTGCCTCAGACCTGCCAATGTCCCCCAGAGGGCCTACCTAGAGCAAAT

AATATGACATTTAGAATAAAAGTGATTGGTGACCCCAATCAAGACATCCTTGGATAAGTTGCCCAGACTC

CAGCCTCTCTGGAGCCTCAGTTATTTGATAAAATAATGTCACTTTCCAAATAAGCCACAAAATGCAAATA

CTCATGGCAACCTAAAGCATTATACCCAAACAGTGTCCCTTAGGGCTTGTCCTGTCTATTCTGACTCCTT

TTATATTCAAACTATTTAAACTGCTTGCTTGTGTTGAAGTCCAAATTTCCATTGCGTATGGCTATTGATA

TTTTTGTTTGGAATTTTTTTTTTTTTTTTTTGACACGGAGTTTCACTCTTGCTGCCCAGGCTGGAGTGCA

ATGGCACGATCTCGGGATCTCAGCTCACCGCAACCTCCGCCTCCCGGGTTCAAACAATTCTCCTGCCTCA

GCCTCCCAAGTAGCTGGGATTACAGGCATGTGCCACCACGCCCAGCTAATTTTGTATTTCTAGTAGAGAC

GGGGTTTCTCCATGTTGGTCAGGCTGGTCTCGAACTCCCAACCTCAGGTGATCTGCCTGCTTGGGCCTCC

CAAAGTGCTAGGATTACAGGCGTGAGCCACCGCACCCACCCTGGAATTCTTTGTAAACTCCTTATGGTGC

GAACTAATGTAACTTTCCATCCAGTTATGGGGGATTGGTGCAATTTTAAATTATCACTATGATTTGCTAT

TTCCATTTGAGCAAATTTCCTATAGAGTTTCCTTTCAGTGGACTAGACCCATATCAGGAAGTGACTTAGG

TATAAAGGGAAGATACAGCTTTCGAAAACCAAAGTTTGGGCGTTCTCCAAAGAGTTATCAGATACCCCCT

TCTACACCCACAATGATCTGATTGCTGAGATCTGATTGCTAACTACTGAAAATAAGGAAGAACTAGAATT

TTCAGTGACACAGTGCTCAGCAAGAAGCTAGAAAAGAGGCCTTGACATATTTGACTCCAAAGCTACTTGG

TTATGCATGAAGCCATCTGGGGAGGGGAAGGAGGAGGGAGAACTCCTCTGAGGACCCTGAAACAATTGGG

CCACGTGTGACTTTCAGTTTCTATGGAGATTCATGTGCAGTGGCTGAGGGCAATCTGAGAGCATTGGAAA

CCCAGAAGCTTTAATACCAGGCTCTTCTCTCCGCTCTTAGAAAGTTCTCACAAGATGTCTTTAGGATTAT

ATTGGTTATTTGAATCTCAAGGAGAAGCTCCTCTCACTGCCCTACCTCCCTGAACTGAAAACAAACTGTA

GTCTGTTAGCTCACCCTAGAAGAAGGAAATTCTAGAGTCAAGAGAAGTTAAGTTTTAGACAAGCTGGAAG

TTGGAATATACTGGAGTTTAAGATCATTGACTCAATGAAAAAAAAAAAAGATTTGTCTGCAGTAAAACCA

7. Motif

Pfam(16motifs)

Pfam	Position(Independent E-value)	Description
PK_Tyr_Ser-Thr	402..650(1.2e-97)	PF07714, Protein tyrosine and serine/threonine kinase
Pkinase	404..649(6.5e-48)	PF00069, Protein kinase domain
SH2	281..362(1.3e-21)	PF00017, SH2 domain
SH3_1	220..266(4.6e-17)	PF00018, SH3 domain
PH	5..133(1.3e-12)	PF00169, PH domain
BTK	141..167(3.3e-13)	PF00779, BTK motif
SH3_9	221..270(3e-06)	PF14604, Variant SH3 domain
SH3_2	219..271(4.3e-06)	PF07653, Variant SH3 domain
Kinase-like	508..609(0.00043)	PF14531, Kinase-like
SH3_10	217..266(0.00058)	PF17902, SH3 domain
SH3_3	234..269(0.0013)	PF08239, Bacterial SH3 domain
ABC1	470..546(0.024)	PF03109, ABC1 atypical kinase-like domain
Pkinase_fungal	491..532(0.025)	PF17667, Fungal protein kinase
Kdo	438..533(0.056)	PF06293, Lipopolysaccharide kinase (Kdo/WaaP) family
Haspin_kinase	509..546(0.075)	PF12330, Haspin like kinase domain
SH3_4	250..267(0.27)	PF06347, Bacterial SH3 domain

8. Evolutionary Relationship

Evolutionary analysis by Maximum Likelihood method

The evolutionary history was inferred by using the Maximum Likelihood method and JTT matrix-based model [1]. The tree with the highest log likelihood (-6120.14) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log likelihood value. The proportion of sites where at least 1 unambiguous base is present in at least 1 sequence for each descendent clade is shown next to each internal node in the tree. This analysis involved 100 amino acid sequences. There were a total of 1010 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE NAME	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs28935478	100613318	Y361C	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.001	2.57	DELETERIOUS
rs41310709	100611100	C502W	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.62	DELETERIOUS
rs41310709	100611100	C502*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs104894770	100608923	R562P	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.001	2.57	DELETERIOUS
rs104894770	100608923	R386P	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.002	2.56	DELETERIOUS
rs128620183	100609675	R525Q	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.57	DELETERIOUS
rs128620183	100609675	R349Q	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.004	2.56	DELETERIOUS
rs128620184	100611833	K430E	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.002	2.57	DELETERIOUS
rs128620185	100630190	R28H	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.59	DELETERIOUS
rs128620185	100630190	R28H	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.56	DELETERIOUS
rs128620186	100630271	M1T	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	3.48	DELETERIOUS
rs128620186	100630271	M1T	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	3.62	DELETERIOUS (WARNING LOW CONFIDENCE)
rs128620187	100630236	R13*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128620187	100630236	R13*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128620188	100630230	Q15*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128620188	100630230	Q15*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128620189	100630176	T33P	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.002	2.56	DELETERIOUS
rs128620189	100630176	T33P	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.004	2.59	DELETERIOUS
rs128621190	100625039	V113D	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.58	DELETERIOUS
rs128621190	100625039	V113D	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.56	DELETERIOUS
rs128621191	100615614	E240*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621191	100615614	E240*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128621192	100615577	W252*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621192	100615577	W252*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128621193	100615569	R255*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621193	100615569	R255*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128621194	100614313	R288W	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.58	DELETERIOUS
rs128621194	100614313	R288W	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.55	DELETERIOUS
rs128621195	100613660	R307G	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.002	2.56	DELETERIOUS
rs128621195	100613660	R307G	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.004	2.57	DELETERIOUS
rs128621196	100613399	Y334S	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.001	2.56	DELETERIOUS
rs128621196	100613399	Y334S	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.003	2.6	DELETERIOUS
rs128621197	100612549	Y375*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621198	100611898	L408P	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.001	2.57	DELETERIOUS
rs128621199	100611846	Y425*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621200	100611090	C506R	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.002	2.57	DELETERIOUS
rs128621201	100611048	R520*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128621202	100611047	R520Q	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.57	DELETERIOUS
rs128621203	100609624	L542P	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.001	2.57	DELETERIOUS
rs128621203	100609624	L366P	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.001	2.56	DELETERIOUS
rs128621204	100608924	R562W	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.57	DELETERIOUS
rs128621204	100608924	R386W	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.56	DELETERIOUS
rs128621205	100608867	W581R	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.57	DELETERIOUS
rs128621205	100608867	W405R	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.56	DELETERIOUS
rs128621206	100608324	E589G	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.55	DELETERIOUS
rs128621206	100608324	E413G	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.54	DELETERIOUS
rs128621208	100608270	A607D	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.56	DELETERIOUS
rs128621208	100608270	A431D	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.001	2.55	DELETERIOUS
rs128621209	100608252	G613D	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.56	DELETERIOUS
rs128621209	100608252	G437D	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.55	DELETERIOUS
rs128621210	100608201	M630K	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0	2.58	DELETERIOUS
rs128621210	100608201	M454K	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0	2.55	DELETERIOUS
rs128622211	100608184	E636*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176
rs128622211	100608184	E460*	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971
rs128622212	100604898	L652P	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176	0.267	2.74	TOLERATED
rs128622212	100604898	L476P	BTK	ENSG00000010671	ENST00000372880	ENSP00000361971	0.269	2.71	TOLERATED
rs193922124	100611151	Y485*	BTK	ENSG00000010671	ENST00000308731	ENSP00000308176

Evolutionary analysis of coding SNPs

SNP	substitution	probability of deleterious effect	Pdel
rs28935478	Y361C	probably damaging	0.85
rs41310709	C502W	probably damaging	0.74
rs41310709	R562P	probably damaging	0.57
rs104894770	R525Q	probably damaging	0.85
rs128620183	K430E	probably damaging	0.85
rs128620184	R28H	probably damaging	0.74
rs128620185	R28H	probably damaging	0.74
rs128620185	M1T	probably damaging	0.74
rs128620186	M1T	probably damaging	0.74
rs128620186	T33P	probably damaging	0.74
rs128620187	T33P	probably damaging	0.74
rs128620187	V113D	probably damaging	0.57
rs128620188	V113D	probably damaging	0.57
rs128620188	R288W	probably damaging	0.85
rs128620189	R288W	probably damaging	0.85
rs128620189	R307G	probably damaging	0.85
rs128621190	R307G	probably damaging	0.85
rs128621190	Y334S	probably damaging	0.85
rs128621191	Y334S	probably damaging	0.85
rs128621191	L408P	probably damaging	0.85
rs128621192	C506R	probably damaging	0.85
rs128621192	R520Q	probably damaging	0.85
rs128621193	L542P	probably damaging	0.57
rs128621194	R562W	probably damaging	0.57
rs128621195	W581R	probably damaging	0.85
rs128621196	E589G	probably damaging	0.85
rs128621197	A607D	possibly damaging	0.5
rs128621199	G613D	probably damaging	0.85
rs128621201	M630K	probably damaging	0.85
rs128621203	L652P	possibly damaging	0.5

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs28935478	Y361C	Damaging	Deleterious	-8.71
rs41310709	C502W	Damaging	Deleterious	-10.6
rs104894770	R562P	Damaging	Deleterious	-4.37
rs104894770	R386P	Damaging	Deleterious	-4.45
rs128620183	R525Q	Damaging	Deleterious	-3.97
rs128620183	R349Q	Damaging	Deleterious	-3.61
rs128620184	K430E	Damaging	Deleterious	-3.9
rs128620185	R28H	Damaging	Deleterious	-4.49
rs128620185	R28H	Damaging	Deleterious	-4.27
rs128620186	M1T	Damaging	Deleterious	-0.07
rs128620186	M1T	Damaging	Deleterious	-0.17
rs128620189	T33P	Damaging	Deleterious	-4.58
rs128620189	T33P	Damaging	Deleterious	-4.78
rs128621190	V113D	Damaging	Deleterious	-6.03
rs128621190	V113D	Damaging	Deleterious	-6.09
rs128621194	R288W	Damaging	Deleterious	-7.51
rs128621194	R288W	Damaging	Deleterious	-6.97
rs128621195	R307G	Damaging	Deleterious	-5.93
rs128621195	R307G	Damaging	Deleterious	-6.79
rs128621196	Y334S	Damaging	Deleterious	-7.04
rs128621196	Y334S	Damaging	Deleterious	-8.74
rs128621198	L408P	Damaging	Deleterious	-6.54
rs128621200	C506R	Damaging	Deleterious	-9.51
rs128621202	R520Q	Damaging	Deleterious	-3.96
rs128621203	L542P	Damaging	Deleterious	-4.96
rs128621203	L366P	Damaging	Deleterious	-4.51
rs128621204	R562W	Damaging	Deleterious	-6.01
rs128621204	R386W	Damaging	Deleterious	-5.89
rs128621205	W581R	Damaging	Deleterious	-13.89
rs128621205	W405R	Damaging	Deleterious	-12.89
rs128621206	E589G	Damaging	Deleterious	-6.91
rs128621206	E413G	Damaging	Deleterious	-6.68
rs128621208	A607D	Damaging	Deleterious	-3.04
rs128621208	A431D	Damaging	Deleterious	-3.06
rs128621209	G613D	Damaging	Deleterious	-6.68
rs128621209	G437D	Damaging	Deleterious	-6.47
rs128621210	M630K	Damaging	Deleterious	-5.52
rs128621210	M454K	Damaging	Deleterious	-5.17
rs128622212	L652P	Tolerated	Neutral	-0.54
rs128622212	L476P	Tolerated	Neutral	-0.85

SNAP2

Wildtype amino acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accuracy
C	502	W	Effect	75	95%
R	562	P	Effect	29	95%
R	386	P	Effect	87	95%
R	525	Q	Effect	56	95%
R	349	Q	Effect	34	95%
K	430	E	Effect	78	95%
R	28	H	Effect	90	95%
R	28	H	Neutral	45	85%
M	1	T	Effect	75	85%
M	1	T	Effect	34	85%
T	33	p	Effect	67	85%
T	33	P	Effect	98	65%
V	113	D	Effect	12	65%
V	113	D	Effect	79	65%
R	228	W	Effect	34	65%
R	228	W	Effect	87	65%
R	228	W	Neutral	76	95%
R	307	G	Effect	34	75%
Y	334	S	Effect	78	65%
Y	334	S	Effect	12	85%
L	408	P	Effect	78	65%
C	506	R	Effect	90	85%
R	520	Q	Neutral	56	75%
L	542	P	Neutral	65	45%
L	366	P	Neutral	89	85%
R	562	W	Effect	76	95%
R	386	W	Effect	45	85%
W	581	R	Effect	34	65%
W	405	E	Effect	-29	45%
E	589	G	Effect	67	25%
E	413	G	Effect	35	95%
A	607	D	Effect	65	85%
A	431	D	Neutral	75	75%
G	613	D	Effect	98	55%
G	437	D	Neutral	85	45%
M	630	K	Effect	45	76%
M	454	K	Effect	-26	46%
L	652	P	Effect	75	76%
L	476	P	Neutral	76	47%

Polyphone 2

Rs_Id	Mutation Probability	Score
rs28935478	Probably damaging	0.999
rs41310709	Probably damaging	0.999
rs104894770	Probably damaging	0.98
rs104894770	Possibly damaging	1.00
rs128620183	Possibly damaging	0.999
rs128620183	Probably damaging	0.999
rs128620184	Probably damaging	0.999
rs128620185	Probably damaging	0.98
rs128620185	Possibly damaging	1.00
rs128620186	Possibly damaging	0.999
rs128620186	Possibly damaging	1.00
rs128620189	Possibly damaging	0.999
rs128620189	Probably damaging	0.999
rs128621190	Probably damaging	0.98
rs128621190	Possibly damaging	1.00
rs128621194	Possibly damaging	0.999
rs128621194	Probably damaging	0.999
rs128621195	Possibly damaging	1.00
rs128621195	Possibly damaging	0.999
rs128621196	Probably damaging	0.999
rs128621196	Probably damaging	0.999
rs128621198	Probably damaging	0.999
rs128621200	Probably damaging	0.98
rs128621202	Possibly damaging	1.00
rs128621203	Probably damaging	0.999
rs128621203	Probably damaging	0.999
rs128621204	Probably damaging	0.98
rs128621204	Possibly damaging	1.00
rs128621205	Probably damaging	1.00
rs128621205	Probably damaging	0.98
rs128621206	Possibly damaging	1.00
rs128621206
rs128621208	Probably damaging	0.999
rs128621208	Probably damaging	0.98
rs128621209	Possibly damaging	1.00
rs128621209	Probably damaging	0.999
rs128621210	Probably damaging	0.999
rs128621210	Probably damaging	0.98
rs128622212	Possibly damaging	1.00
rs128622212	Possibly damaging	1.00

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs28935478	BTK_Y361C	Uniprot Residue:G	Y361C	High	6.33
rs41310709	BTK_C502W		C502W	Low	1.12
rs104894770	BTK_R562P		R562P	Medium	4.3
rs104894770	BTK_R386P		R386P	Low	0.65
rs128620183	BTK_R525Q	Uniprot Residue:C	R525Q	High	6.62
rs128620183	BTK_R349Q		R349Q	Medium	2.16
rs128620184	BTK_K430E		K430E	Medium	4.3
rs128620185	BTK_R28H		R28H	Low	0.32
rs128620186	BTK_M1T		M1T	High	10.5
rs128620189	BTK_T33P	Uniprot Residue:I	T33P	Medium	3.35
rs128621190	BTK_V113D		V113D	Medium	4.56
rs128621194	BTK_R288W		R288W	High	5.94
rs128621195	BTK_R307G		R307G	High	10.6
rs128621196	BTK_Y334S	Uniprot Residue:N	Y334S	Low	1.5
rs128621198	BTK_L408P		L408P	Medium	2.82
rs128621200	BTK_C506R		C506R	low	4.56
rs128621202	BTK_R520Q		R520Q	High	5.94
rs128621203	BTK_L542P		L542P	High	10.6
rs128621204	BTK_R562W		R562W	High	10.5
rs128621204	BTK_R386W		R386W	Medium	4.62
rs128621205	BTK_W581R	Uniprot Residue:M	W581R	Medium	3.56
rs128621205	BTK_W405R		W405R	Medium	2.22
rs128621206	BTK_E589G		E589G	Medium	4.64
rs128621206	BTK_E413G		E413G	High	5.94
rs128621208	BTK_A607D		A607D	Medium	4.82
rs128621208	BTK_A431D		A431D	Medium	2.16
rs128621209	BTK_G613D		G613D	High	5.52
rs128621209	BTK_G437D	Uniprot Residue:L	G437D	High	6.73
rs128621210	BTK_M630K		M630K	Medium	2.16
rs128621210	BTK_M454K		M454K	High	6.88
rs128622212	BTK_L652P		L652P	High	6.92
rs128622212	BTK_L476P	Uniprot Residue:T	L476P	Low	0.45

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	0.77	658	2uztA	SS3	408,409,410,416,428, 430,458,474,475,476, 477,481,525,526,528, 538,539
2	0.09	85	3f6xA	IHH	408,416,428,430,474, 475,476,477,478,480,528,539
3	0.07	104	3f82A	353	408,416,428,430,442,445,449,452, 457,458,472,474,475,476,477,512, 517,519,528,537,538,539,540
4	0.05	29	3c51B	MG	526,539
5	0.01	19	1rqqA	PEPTIDE	412,525,554,555,556,557,558,559, 560,561,563,569,570,571,572,603, 607,611
6	0.01	18	3pyyB	3YY	495,498,499,502,587,590,591,620, 621,622,623,626
7	0.01	10	2c0tB	CA	430,526,539
8	0.00	2	2x2mA	FMT	520,542,553,557,558,559
9	0.00	1	3dqwB	MG	525,526
10	0.00	1	2p0cB	MG	510,514,645

11. Primary Sequence Analysis

Number of amino acids

659

Molecular weight

76281.24

Theoretical pI

7.83

Amino acid composition

Top of Form

Ala (A) 29 4.4%

Arg (R) 34 5.2%

Asn (N) 23 3.5%

Asp (D) 27 4.1%

Cys (C) 12 1.8%

Gln (Q) 32 4.9%

Glu (E) 58 8.8%

Gly (G) 36 5.5%

His (H) 15 2.3%

Ile (I) 34 5.2%

Leu (L) 57 8.6%

Lys (K) 53 8.0%

Met (M) 20 3.0%

Phe (F) 24 3.6%

Pro (P) 37 5.6%

Ser (S) 54 8.2%

Thr (T) 26 3.9%

Trp (W) 11 1.7%

Tyr (Y) 37 5.6%

Val (V) 40 6.1%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

(B) 0 0.0%

(Z) 0 0.0%

(X) 0 0.0%

Bottom of Form

Total number of negatively charged residues (Asp + Glu)

Total number of positively charged residues (Arg + Lys)

Formula

C₃₄₂₄H₅₃₁₀N₉₁₀O₁₀₀₂S₃₂

Total number of atoms()

10678

Instability index(II)

53.15

Stability

unstable

Aliphatic index(AI)

75.86

GRAVY

-0.555

12. Secondary structure analysis

Alpha helix (Hh) : 175 is 26.56%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 114 is 17.30%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 370 is 56.15%

Ambiguous states (?) : 0 is 0.00%

Other states : 0 is 0.00%

Secondary Structure Prediction

Amino Acid Type

13. Enzymes

Name of enzyme	No. of cleavages
Arg-C proteinase	34
Asp-N endopeptidase	27
Asp-N endopeptidase + N-terminal Glu	85
BNPS-Skatole	11
CNBr	20
Chymotrypsin-high specificity (C-term to [FYW], not before P)	68
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	150
Clostripain	34
Formic acid	27
Glutamylendopeptidase	58
Hydroxylamine	3
Iodosobenzoic acid	11
LysC	53
LysN	53
NTCB (2-nitro-5-thiocyanobenzoic acid)	12
Pepsin (pH1.3)	113
Pepsin (pH>2)	175
Proline-endopeptidase	7
Proteinase K	316
Staphylococcal peptidase I	52
Thermolysin	164
Trypsin	80

14. Epitope

Rank	Start Position	Sequence	Score	Prediction
1	69	PEKNPPPERQIPRRGEESSE	1	Epitope
1	196	QILKKPLPPEPAAAPVSTSE	1	Epitope
1	175	LKPGSSHRKTKKPLPPTPEE	0.998	Epitope
1	375	YPVSQQNKNAPSTAGLGYGS	0.997	Epitope
1	296	KQEGKEGGFIVRDSSKAGKY	0.989	Epitope
1	317	VSVFAKSTGDPQGVIRHYVV	0.973	Epitope
2	626	VYTIMYSCWHEKADERPTFK	0.956	Epitope
2	564	SPPEVLMYSKFSSKSDIWAF	0.951	Epitope
2	255	RDKNGQEGYIPSNYVTEAED	0.929	Epitope
2	409	GTGQFGVVKYGKWRGQYDVA	0.929	Epitope
2	454	HEKLVQLYGVCTKQRPIFII	0.911	Epitope
3	485	YLREMRHRFQTQQLLEMCKD	0.91	Epitope
2	38	SYYEYDFERGRRGSKKGSID	0.834	Epitope
2	98	FPYPFQVVYDEGPLYVFSPT	0.834	Epitope
2	135	NSDLVQKYHPCFWIDGQYLC	0.798	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	38
Avg node degree	6.91
avg. local clustering coefficient	0.849
expected number of edges	11
p-value	2.73e-10
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot